Article
Chemistry, Multidisciplinary
Mateusz Dyguda, Artur Przydacz, Lukasz Albrecht
Summary: This manuscript describes the application of dearomative formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines. The developed approach utilizes aminocatalytic activation of 2-alkyl-3-furfurals that proceeds via formation of the dearomatized dienamine intermediate. The obtained cycloadducts can be further transformed into tetrahydrofuropyridines or functionalized cinnamates.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Mateusz Dyguda, Artur Przydacz, Lukasz Albrecht
Summary: This manuscript describes the application of dearomative formal normal-electron-demand aza-Diels-Alder cycloaddition in the synthesis of tetrahydrofuropyridines. The method involves the aminocatalytic activation of 2-alkyl-3-furfurals and proceeds via the formation of dearomatized dienamine intermediate. The obtained cycloadducts can be further transformed into tetrahydrofuropyridines or functionalized cinnamates. The mechanism of the transformation was confirmed through DFT calculations.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Organic
Simranpreet K. Wahan, Gaurav Bhargava, Pooja A. Chawla
Summary: Ultrasound is an eco-friendly and cost-effective technique that has attracted interest from chemists for its ability to reduce reaction time and the use of hazardous chemicals, and enhance compound purity. The application of ultrasound waves as a non-polluting energy source has great importance in the field of green and sustainable chemistry. This review focuses on the latest applications of ultrasonication in the preparation of oxygen and nitrogen-containing heterocycles, which play an important role in therapeutically active molecules and will assist new researchers in their ongoing and future research.
CURRENT ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Licheng Wu, Jingping Qu, Yifeng Chen
Summary: Here, a Pd-catalyzed isomerization of alicyclic allyl amine to achieve alpha, beta-difunctionalization of synthetically inaccessible trisubstituted cyclic enamine is reported. The in situ formed enamine intermediate plays a dual role, enabling intermolecular formal [4 + 2] reaction with acrylamide or isatoic anhydride to simultaneously construct C-C and C-N bonds, leading to the expedient construction of [4.3.0]-aminal with excellent diastereoselectivity and high atom economy.
Review
Chemistry, Multidisciplinary
Vladimir V. Chernyshov, Irina I. Popadyuk, Olga Yarovaya, Nariman F. Salakhutdinov
Summary: The directed transformation of available natural compounds is a promising research area in organic and medicinal chemistry for finding effective drug substances. This review aims to summarize the literature data on the preparation and properties of nitrogen-containing heterocyclic compounds synthesized from monoterpenes/monoterpenoids and their nearest derivatives from 2000 to 2021.
TOPICS IN CURRENT CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Elzbieta Regulska, Philip Hindenberg, Adrian Espineira-Gutierrez, Carlos Romero-Nieto
Summary: Linearly-fused diphosphaarenes are a novel family of molecules with striking optoelectronic properties and outstanding stability, which hold great importance in materials science.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Applied
Amalia-Sofia Piticari, Daniele Antermite, Joe Higham, J. Harry Moore, Matthew P. Webster, James A. Bull
Summary: This study achieved the selective Pd-catalyzed C-H cis-functionalization of piperidine and tetrahydropyran carboxylic acids using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity was obtained by adding mesityl carboxylic acid. The reaction conditions developed in this study had significantly lower temperatures compared to other reported heterocycle C(sp(3))-H functionalization reactions, and a one-pot C-H functionalization-epimerization procedure was established to directly obtain the trans-3,4-disubstituted isomers. Diverse aminoquinoline removals were achieved by installing carboxylic acid, alcohol, amide, and nitrile functional groups. Overall, fragment compounds suitable for screening were synthesized in 3-4 steps from readily-available heterocyclic carboxylic acids.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Kaivin Hadidi, Yitzhak Tor
Summary: Analogues of N,N-dimethyladenine with thieno- and isothiazolo-pyrimidine cores were modified using 3-substituted azetidines to produce fluorescent fluorophores with high emission quantum yields. The substituents on the azetidine ring correlated with the emission quantum yields. Ribosylation of the modified nucleobase resulted in a lower emission quantum yield in water compared to the precursor nucleobase, but the high emission quantum yield was restored in deuterium oxide, indicating the potential impact of the sugar moiety on the photophysical features of fluorescent nucleosides.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Mohammed Sharique, Jadab Majhi, Roshan K. Dhungana, Lisa Marie Kammer, Matthias Krumb, Alexander Lipp, Eugenie Romero, Gary A. Molander
Summary: In this study, a simple, open-air, and efficient light-mediated Minisci C-H alkylation method is described, which is based on the formation of an electron donor-acceptor complex. Unlike previous protocols, this method does not require a photocatalyst, single electron transfer agent, or oxidant additive. The reaction can proceed under mildly acidic and open-air conditions, and it yields moderate to good amounts of Minisci alkylation products.
Article
Chemistry, Multidisciplinary
Kateryna Fominova, Taras Diachuk, Dmitry Granat, Taras Savchuk, Vladyslav Vilchynskyi, Oleksiy Svitlychnyi, Vladyslav Meliantsev, Igor Kovalchuk, Eduard Litskan, Vadym V. Levterov, Valentyn R. Badlo, Ruslan Vaskevych, Alla Vaskevych, Andrii Bolbut, Volodymyr V. Semeno, Rustam Iminov, Kostiantyn Shvydenko, Anastasiia S. Kuznetsova, Yurii Dmytriv, Daniil Vysochyn, Vasyl Ripenko, Andrei A. Tolmachev, Olexandra Pavlova, Halyna Kuznietsova, Iryna Pishel, Petro Borysko, Pavel K. Mykhailiuk
Summary: A general method for synthesizing oxa-spirocycles was developed using iodocyclization, resulting in over 150 compounds. Incorporation of an oxygen atom into the spirocyclic unit significantly improved water solubility and decreased lipophilicity. More potent oxa-spirocyclic analogues of the antihypertensive drug terazosin were synthesized and evaluated in vivo.
Article
Chemistry, Multidisciplinary
Yongzhi Hu, Huiqing Hou, Ling Yu, Sunying Zhou, Xianghua Wu, Weiming Sun, Fang Ke
Summary: The oxidative tandem cyclization of primary alcohols with 2-aminobenzamides to synthesize quinazolinones using K2S2O8 as a radical surrogate under undivided electrolytic conditions is a green, mild, and practical method with high efficiency and excellent functional group tolerance. The use of continuous-flow electrochemical setups allows for easy scalability of the reaction.
Article
Chemistry, Multidisciplinary
Matthew L. Martin, Claire Wilson, Alistair Boyer
Summary: Unsaturated N-2-sulfonyl amidines are converted into valuable N-heterocyclic products through heating with BF2OTf. Mechanistic studies suggest a domino 1,7-H shift that activates a C-H bond, followed by electrocylisation, resulting in stereodefined cyclic amidines.
CHEMICAL COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Tuyen N. Tran, Maged Henary
Summary: This review focuses on the synthesis and application of antiviral agents derived from various nitrogen-containing heterocycles in the past decade. These agents have shown broad-spectrum interference against HIV, HCV/HBV, VZV/HSV, SARS-CoV, COVID-19, and influenza viruses, making them promising candidates for antiviral drug development.
Article
Chemistry, Multidisciplinary
Till Drennhaus, Dirk Leifert, Jessika Lammert, Jan Philipp Drennhaus, Klaus Bergander, Constantin G. Daniliuc, Armido Studer
Summary: Enantioenriched chiral indoles were synthesized through a mild and efficient radical cascade reaction. The targeted indoles were accessed by stereochemical control using a chiral copper-bisoxazoline complex. The method demonstrated excellent enantioselectivity and good yields, and the mechanism was elucidated through mechanistic studies.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Till Drennhaus, Dirk Leifert, Jessika Lammert, Jan Philipp Drennhaus, Klaus Bergander, Constantin G. Daniliuc, Armido Studer
Summary: In this study, enantioenriched chiral indoles were synthesized through a mild and efficient radical cascade reaction using a chiral copper-bisoxazoline complex. The targeted 2-fluoroalkylated 3-(alpha-cyanobenzy-lated) indoles were accessed with excellent enantioselectivity and good yields. Mechanistic studies revealed a negative nonlinear effect which explained the stereochemical outcome. The enantioenriched 3-(alpha-cyanobenzylated) indoles demonstrated scalability and potential utility as hubs for chiral tryptamines, indole-3-acetic acid derivatives, and triarylmethanes, and a formal synthesis of a natural product analogue was disclosed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Bijay Shrestha, Brennan T. Rose, Casey L. Olen, Aaron Roth, Adon C. Kwong, Yang Wang, Scott E. Denmark
Summary: A general procedure for asymmetric synthesis of highly substituted 1,2-amino alcohols has been described, utilizing organometallic additions as the key step. Diastereoselectivity in these reactions significantly depends on the nucleophile and electrophile involved. The resulting amino alcohols are further used to synthesize stereochemically diverse polysubstituted 2,2'-methylene(bisoxazoline) ligands in high yields.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
N. Ian Rinehart, Andrew F. Zahrt, Jeremy J. Henle, Scott E. Denmark
Summary: The design of catalysts in enantioselective catalysis is traditionally based on empirical methods. This study introduces a more quantitative approach by defining a library of catalyst permutations, using 3D representations and statistical learning tools to predict catalyst function and optimize catalyst performance. Through iterative experimental testing and refinement of statistical models, a systematic workflow for catalyst design and optimization is established for various reactions within a given chemical space.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Organic
Andrew F. Zahrt, N. Ian Rinehart, Scott E. Denmark
Summary: This study developed and applied a new steric descriptor for generating models that relate catalyst performance to catalyst structure in enantioselective transformations, demonstrating its generality and interpretability across different reactions. The low dimensionality and ability to capture conformational effects make it well-suited for creating Quantitative Structure-Selectivity Relationships with smaller datasets of asymmetric reactions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Scott J. Barraza, Janice A. Sindac, Craig J. Dobry, Philip C. Delekta, Pil H. Lee, David J. Miller, Scott D. Larsen
Summary: This study focused on the design, synthesis, and evaluation of a series of conformationally restricted analogues with the goal of improving potency/selectivity and identifying the most bioactive conformation. While the campaign had only modest success in improving potency, the rigid analogs defined a three-dimensional pharmacophore, which is believed to be valuable for future analog design and virtual screening for alternative antiviral leads.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
N. Ian Rinehart, Andrew F. Zahrt, Scott E. Denmark
Summary: Traditional catalyst optimization methods are limited and inefficient, so we have developed an informatics-guided workflow utilizing artificial intelligence and machine learning to accelerate catalyst discovery and optimization, as well as to identify high-performing catalysts.
Article
Chemistry, Multidisciplinary
Vincent M. Kassel, Christopher M. Hanneman, Connor P. Delaney, Scott E. Denmark
Summary: Reaction conditions have been developed for refractory heteroaryl-heteroaryl Suzuki-Miyaura cross-couplings using neopentyl heteroarylboronic esters, heteroaryl bromides and chlorides, and potassium trimethylsilanolate (TMSOK) under anhydrous conditions. The addition of trimethyl borate enhances reaction rates by several mechanisms, enabling cross-coupling of diverse reaction partners in good yields and short reaction times.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Emily M. Mumford, Brett N. Hemric, Scott E. Denmark
Summary: This study reports a method for the chemo-, regio-, diastereo-, and enantioselective oxyamination of alkenes using selenium(II/IV) catalysis with a chiral diselenide catalyst. The reaction demonstrates good yields and excellent enantio- and diastereoselectivity for a variety of alkenes and different functional groups. The use of N-tosylamides to generate oxazoline products allows for the assembly of chiral ligands and various protected amino alcohols in an expedited manner.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Chemistry, Organic
Zhong-Lin Tao, Scott E. Denmark
Summary: Enantioselective diamination of alkenes is an important method for accessing enantioenriched, vicinal diamines, with broad applications in asymmetric synthesis. Despite lagging behind dihydroxylation of olefins, successful methods using different reaction mechanisms have been developed for enantioselective olefin diamination. This review highlights recent advances and limitations in the field, aiming to inspire further developments.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Organic
Kimberly M. Hilby, Scott E. Denmark
Summary: A Lewis base catalyzed, enantioselective sulfenocyclization of alkenes to afford [6,6]spiroketals has been developed with excellent yields and enantioselectivities. The method allows for rapid formation of highly substituted spiroketals using a chiral Lewis base catalyst and electrophilic sulfur source.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Applied
Katrina W. Lexa, Kevin M. Belyk, Jeremy Henle, Bangping Xiang, Robert P. Sheridan, Scott E. Denmark, Rebecca T. Ruck, Edward C. Sherer
Summary: Molecular design benefits from the partnership between chemical intuition and machine learning. In this study, different methods for modeling a catalyst system were investigated, and it was found that the 2D random forest approach outperformed other methods. With the passage of time, the model performance improved, and a high-throughput approach was crucial for large-scale optimization.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Article
Chemistry, Multidisciplinary
Connor P. Delaney, Daniel P. Marron, Alexander S. Shved, Richard N. Zare, Robert M. Waymouth, Scott E. Denmark
Summary: Previous studies have shown that the critical transmetalation step in the Suzuki-Miyaura cross-coupling occurs through the oxo-palladium pathway. However, this study demonstrates that the reaction can proceed through the boronate pathway when potassium trimethylsilanolate is used as a promoter. Additionally, a novel binuclear palladium complex was discovered and its role in the catalytic cycle was confirmed.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Anastassia Matviitsuk, Jesse Lee Panger, Scott E. Denmark
Summary: This study reports a chiral selective method for the sulfenofunctionalization of cyclic and (Z)-alkenes, correcting previous findings through experimental results and demonstrating the different behavior of (Z)-alkenes compared to their more established (E)-counterparts.
Article
Chemistry, Multidisciplinary
Brennan T. Rose, Jacob C. Timmerman, Seth A. Bawel, Steven Chin, Haiming Zhang, Scott E. Denmark
Summary: The atropselective iodination of 2-amino-6-arylpyridines catalyzed by chiral disulfonimides is achieved using a curated training set of catalysts obtained through a chemoinformatic workflow. Data fusion techniques are employed to predict catalyst performance when linear regression analysis fails. A privileged class of alkynyl-DSI catalysts is identified, demonstrating high stereoselectivity and generality in the iodination of various 2-amino-6-arylpyridines. Preparative-scale demonstrations show the utility of this reaction with high enantioselectivity and good chemical yield.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Andrew F. Zahrt, Brennan T. Rose, William T. Darrow, Jeremy J. Henle, Scott E. Denmark
Summary: This study examines the application of machine learning in homogeneous catalysis and methods for optimizing catalysts. It compares different approaches for training set selection and assessment of prediction confidence, while demonstrating the generality of ASO and AEIF descriptors in transition metal catalysts.
REACTION CHEMISTRY & ENGINEERING
(2021)
Article
Polymer Science
Anja R. A. Palmans, E. W. Meijer, Scott E. Denmark
Summary: Stereochemical nomenclature is a point of attention as different fields in chemistry become more entwined. Amplification of asymmetry is recommended as an alternative to amplification of chirality, referring to the increase of asymmetry in enantiomeric composition at the molecular or supramolecular level. This covers the nonproportional increase in optical activity in helical polymers and high enantiomeric excesses found in asymmetric catalysis with nonlinear effects.
JOURNAL OF POLYMER SCIENCE
(2021)